Captopril kinetics in chronic congestive heart failure

We investigated the kinetics of 25 mg captopril by mouth in 12 patients with congestive heart failure and correlated them with the hormonal and hemodynamic changes associated with the drug. Observations were made after a single dose (25 mg orally), and after short-term therapy (25 mg t.i.d. for 3 days). Captopril kinetics were as previously reported in normal subjects, with the exception that time to maximum concentration (tmax) to free captopril was slightly higher and the half-life (t1/2) was slightly shorter than in normal subjects. Total captopril t1/2 was longer than normal, suggesting cumulation. Urinary excretion was slower than normal. Differences between captopril kinetics on days 1 and 5 were that the tmax developed somewhat sooner, with a shorter t1/2 on day 5 and total captopril blood levels were higher on day 5 than on day 1. Urinary excretion was greater on day 5 than on day 1. Hemodynamic improvement after a single oral dose of captopril was significant and correlated with baseline plasma renin activity (PRA). The onset of converting-enzyme inhibition, as determined by PRA and hemodynamic improvement correlated with captopril blood levels.